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IFN-alpha-induced motor slowing is associated with increased depression and fatigue in patients with chronic hepatitis C
Open accessAbstract
Interferon (IFN)-alpha has been used to investigate pathways by which innate immune cytokines influence the brain and behaviour. Previous studies suggest that altered basal ganglia function may contribute to IFN-alpha-induced neuropsychological and behavioural changes. To further examine IFN-alpha effects on neuropsychological functions related to basal ganglia (as well as other brain regions), and explore the relationship between altered neuropsychological function and IFN-alpha-induced depression and fatigue, a selected subset of the Cambridge Neuropsychological Test Automated Battery was administered to 32 hepatitis C patients at baseline (Visit 1) and following approximately 12 weeks (Visit 2) of either no treatment (n=12) or treatment with IFN-alpha plus ribavirin (n=20). Symptoms of depression and fatigue were assessed using the Montgomery-Asberg Depression Rating Scale and the Multidimensional Fatigue Inventory. Compared to control subjects, patients treated with IFN-alpha/ribavirin exhibited significant decreases in motor speed as measured in the simple and five-choice movement segments of the CANTAB reaction time task and slower response times in the rapid visual information processing task, a task of sustained attention. Decreased motor speed on the five-choice movement segments of the reaction time task was in turn correlated with increased symptoms of depression and fatigue (R=0.47, p<0.05 and R=0.48, p<0.05, respectively). IFN-alpha/ribavirin treatment had no effects on executive function, decision time in the reaction time task, or target detection accuracy in the sustained attention task. Motor slowing and its correlation with psychiatric symptoms suggest that altered basal ganglia function may contribute to the pathogenesis of IFN-alpha-induced behavioural changes.
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“This study used IFN-α (plus ribavirin) as an inflammatory stimulus and measured planning ability with the Stockings of Cambridge task, and no effect of inflammation on planning ability was observed (Majer et al., 2008).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Majer et al., 2008
In the citing paper
“IFN-α (plus ribavirin) therapy led to significant decreases in motor speed among patients with hepatitis C (Majer et al., 2008).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Majer et al., 2008
In the citing paper
“Notably, decreased motor speed in this study was also associated with increased symptoms of depression and fatigue (Majer et al., 2008).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Majer et al., 2008
In the citing paper
“Notably, decreased motor speed in this study was also associated with increased symptoms of depression and fatigue (Majer et al., 2008).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Majer et al., 2008
In the citing paper
“The fatigue of depression, which is often a residual symptom of SSRI therapy, is a prominent feature of cytokine-induced depression, and may represent cytokine effects on the basal ganglia and dopamine (DA) function (Capuron et al., 2001, Majer et al., 2008, Capuron et al., 2009).”
From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Majer et al., 2008
In the citing paper
“depression and fatigue are the main side effects of treatment with IFN-α (111, 112).”
From Cytokine Research in Depression: Principles, Challenges, and Open Questions (2019) · cites this paper as [112]
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Metadata
- Authors
- Majer, M., Welberg, L. A. M., Capuron, L., Pagnoni, G., Raison, C. L., & Miller, A. H.
- Affiliations
- Emory University (US)
- Corresponding author
- Miller, Andrew H.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 22
- Issue
- 6
- Pages
- 870-880
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC2497339
- OpenAlex
- W2058231748
- Cited by
- 124
- References
- 93
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 11 · 2020: 3 · 2019: 8 · 2018: 6 · 2017: 7 · 2016: 13 · 2015: 4 · 2014: 7 · 2013: 4 · 2012: 16
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (UL1TR000454)
- National Heart, Lung, and Blood Institute (R01HL073921)
- National Institute of Mental Health (R01MH067990, K05MH069124)
- National Center for Research Resources (MO-1-RR-00039, M01RR000039)
- NIH Clinical Center
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- interferon-alpha, chronic hepatitis C, motor slowing, depression, fatigue, basal ganglia, neuropsychological outcomes, ribavirin, reaction time, sustained attention
- MeSH terms
- Adult, Antiviral Agents, Basal Ganglia, Depression, Fatigue, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neuropsychological Tests, Prospective Studies, Psychiatric Status Rating Scales, Reaction Time, Regression Analysis, Ribavirin, Interferon-alpha, Hepatitis C, Chronic
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